In vitro modeling of endometriosis and endometriotic microenvironment - Challenges and recent advances.

Endometriosis is a chronic condition with high prevalence in reproductive age women, defined as the growth of endometrial tissue outside the uterine cavity, most commonly on the pelvic peritoneum. The ectopic endometrial lesions exist in a unique microenvironment created by the interaction of epithelial, stromal, endothelial, glandular, and immune cell components, dominated by inflammatory, angiogenic, and endocrine signals. Current research is directed at understanding the complex microenvironment of the lesions and its relationship with different endometriosis stages, phenotypes, and disease symptoms and at the development of novel diagnostic and therapeutic concepts that minimalize the undesirable side effects of current medical management. Recreating pathophysiological cellular and molecular mechanisms and identifying clinically relevant metrics to assess drug efficacy is a great challenge for the experimental disease models. This review summarizes the complete range of available in vitro experimental systems used in endometriotic studies, which reflect the multifactorial nature of the endometriotic lesion. The article discusses the simplistic in vitro models such as primary endometrial cells and endometriotic cell lines to heterogeneous 2D co-cultures, and recently more common, 3D systems based on self-organization and controlled assembly, both in microfluidic or bioprinting methodologies. Basic research models allow studying fundamental pathological mechanisms by which menstrual endometrium adheres, invades, and establishes lesions in ectopic sites. The advanced endometriosis experimental models address the critical challenges and unsolved problems and provide an approach to drug screening and medicine discovery by mimicking the complicated behaviors of the endometriotic lesion.